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Sainte-Foy-lès-Lyon, France

Tholance Y.,University of Limoges | Tholance Y.,Limoges University Hospital Center | Barcelos G.,University of Geneva | Dailler F.,Neuro Intensive Care Unit | And 4 more authors.
ACS Chemical Neuroscience | Year: 2015

The functional outcome of patients with subarachnoid hemorrhage is difficult to predict at the individual level. The monitoring of brain energy metabolism has proven to be useful in improving the pathophysiological understanding of subarachnoid hemorrhage. Nonetheless, brain energy monitoring has not yet clearly been included in official guidelines for the management of subarachnoid hemorrhage patients, likely because previous studies compared only biological data between two groups of patients (unfavorable vs favorable outcomes) and did not determine decision thresholds that could be useful in clinical practice. Therefore, this Viewpoint discusses recent findings suggesting that monitoring biomarkers of brain energy metabolism at the level of individuals can be used to predict the outcomes of subarachnoid hemorrhage patients. Indeed, by taking into account specific neurochemical patterns obtained by local or global monitoring of brain energy metabolism, it may become possible to predict routinely, and with sufficient sensitivity and specificity, the individual outcomes of subarachnoid hemorrhage patients. Moreover, combining both local and global monitoring improves the overall performance of individual outcome prediction. Such a combined neurochemical monitoring approach may become, after prospective clinical validation, an important component in the management of subarachnoid hemorrhage patients to adapt individualized therapeutic interventions. © 2015 American Chemical Society.

Dorey A.,University Claude Bernard Lyon 1 | Dorey A.,Neurochemistry Unit | Tholance Y.,University of Lyon | Tholance Y.,University of Limoges | And 16 more authors.
JAMA Neurology | Year: 2015

IMPORTANCE: Although typical forms of Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypesmay pose a diagnostic challenge. The major biological diagnostic biomarker for identifying CJD, 14-3-3 protein in cerebrospinal fluid (CSF), unfortunately lacks specificity when confronting a rapid dementia presentation. OBJECTIVE: To assess the relevance of total CSF prion protein (t-PrP) levels in the differential biological diagnosis between atypical AD phenotypes and CJD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study in an autopsy-confirmed cohort of 82 patients was performed to evaluate the relevance of CSF t-PrP to distinguish 30 definite cases of AD from 52 definite cases of CJD. Next, CSF t-PrP concentration was measured in a cohort of 104 patients including 55 patients with probable AD, 26 with probable sporadic CJD, and 23 control patients for whom 14-3-3 protein, total tau, phosphorylated tau 181 (P-tau181), and Aβ1-42 were available. We investigated 46 patients diagnosed as having probable AD who presented atypical phenotypes. A diagnosis strategy was proposed to classify atypical AD phenotypes with suspicion of CJD based on a decision tree combining CSF biomarkers. MAIN OUTCOMES AND MEASURES: We determined CSF t-PrP levels for all patients. We calculated the ratio of total tau and P-tau181 and determined the diagnostic accuracy of each biomarker alone or in combination. We calculated the misclassification rate for each biomarker that corresponded to the percentage of patients within the group of atypical AD phenotypes wrongly classified as CJD. RESULTS: In patients with CJD, CSF t-PrP concentrations were decreased compared with control participants and patients with AD. When considering the differential diagnosis of CJD compared with atypical AD phenotypes, CSF t-PrP determination reached 82.1% sensitivity and 91.3% specificity. The misclassification rate of atypical AD phenotypes decreased from 43.5%, obtained when using the CSF 14-3-3 protein determination alone, to only 4.3% when calculating the ratio total tau/(P-tau181 × t-PrP). The proposed classification tree permitted correct classification of 98.4% of the patients. CONCLUSIONS AND RELEVANCE: For unusual phenotypes of AD, especially cases presenting with a biological ambiguity suggesting CJD, determination of CSF t-PrP levels increased diagnostic accuracy. The use of CSF t-PrP levels may be beneficial in clinical practice in addition to the current classic biomarkers. Copyright 2015 American Medical Association. All rights reserved.

Tholance Y.,Neurochemistry Unit | Tholance Y.,University of Lyon | Barcelos G.K.,University of Lyon | Barcelos G.K.,University of Geneva | And 6 more authors.
Neurological Research | Year: 2015

Objectives: In severe aneurysmal subarachnoid hemorrhage (aSAH), pathological changes in cerebral energy metabolism can be detected either by local measurements using cerebral microdialysis (cMD) together with brain tissue oxygen probe or by global measurements of arterio-jugular difference performed with retrograde jugular vein catheter. Our main objective was to compare the two methods of detection and assess whether combining biomarkers from both procedures could improve outcome prediction, which has never been studied before. Methods: This study included 400 sets of paired arterial and jugular venous samples and 3138 brain microdialyzates obtained from 18 poor-grade aSAH patients. Using Glasgow outcome scale (GOS), neurochemical data from unfavorable (GOS 1–3) and favorable (GOS 4–5) outcome groups were compared. Results: The lactate/pyruvate ratio was found as the most sensitive marker for predicting unfavorable outcome (90%), although not specific. In contrast, hypoxic lactate events and those of metabolic ratio (MR) <3.44, most frequently observed in the unfavorable outcome group than in the favorable one (13.9 vs 0.9% and 33.3 vs 3.75% respectively), were shown to be more specific biomarkers (86%) to predict unfavorable outcome, but less sensitive (<70%). The combination of these three biomarkers improved the accuracy of outcome prediction (sensitivity 90% and specificity 71%). Discussion: Both retrograde jugular venous catheterization (RJVC) and cMD contribute to monitor poor-grade aSAH patients. In this preliminary study, we show that these two techniques are complementary and their combination increases the accuracy of outcome prediction. © W. S. Maney and Son Ltd 2015.

Viaccoz A.,Hospices Civils de Lyon | Viaccoz A.,French Institute of Health and Medical Research | Viaccoz A.,University Claude Bernard Lyon 1 | Ducray F.,Hospices Civils de Lyon | And 22 more authors.
Neuro-Oncology | Year: 2015

Background. The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. Methods. We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. Results. CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P <. 001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P <. 001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P <. 001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. Conclusion Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results. © 2015 The Author(s) 2015.

Barcelos G.K.,University of Lyon | Barcelos G.K.,University of Geneva | Barcelos G.K.,Neurochemistry Unit | Barcelos G.K.,Hopitaux Universitaires Of Geneva | And 9 more authors.
Neurocritical Care | Year: 2013

Purpose: The aim of this study was to determine if the measurement of blood biomarkers of glucose cerebral metabolism, performed with retrograde jugular catheter, could predict the outcome of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients. Methods: This study was conducted in 68 poor-grade aSAH patients. A total of 4,024 blood samples obtained from jugular and radial catheters were analyzed for glucose, lactate, and oxygen content every 8 h for 10 ± 0.5 days. Metabolic ratio (MR) and lactate-oxygen index (LOI) were obtained by ratios using arterio-jugular differences. Functional outcome was evaluated at 12 months with the Glasgow Outcome Scale. Results: Outcome was unfavorable in 40 patients. In this group of patients, the MR was significantly lower (p < 0.0001) and the LOI was significantly higher (p = 0.0001) than in the group with favorable outcome. The MR cutoff value, below which the patients are likely to have an unfavorable outcome, was determined to be 3.35. More interestingly, the data obtained in this study demonstrated that the patients achieving an unfavorable outcome were distinguished from those with a favorable outcome by having at least three events of MR inferior to 3.35 (sensitivity = 90 %, specificity = 82.1 %). Moreover, in patients who developed cerebral vasospasm, we observed a significant decrease in the MR. Conclusion: Our data provide additional support to the view that the MR is a reliable marker for predicting the outcome of poor-grade aSAH patients. Prospective studies are needed to confirm its value in multimodal monitoring. © 2013 Springer Science+Business Media New York.

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